Temporal onset of hypoxia and oxidative stress after pulmonary irradiation
Temporal onset of hypoxia and oxidative stress after pulmonary irradiation
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DOI：
10.1016/j.ijrobp.2006.12.056
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发表时间：
2007-05-01
影响因子：
7
通讯作者：
Vujaskovic, Zeljko
中科院分区：
文献类型：
--
作者：
Fleckenstein, Katharina;Zgonjanin, Larisa;Vujaskovic, Zeljko
目的：探讨照射后肺血管损伤、巨噬细胞聚集、活性氧和细胞因子的产生与缺氧的时间关系。我们以前的研究表明，照射后肺组织的缺氧是导致放射性损伤的原因之一。方法与材料：雌性Fisher 344只大鼠右侧胸腔接受单次28Gy射线照射。连续研究在照射后20周内进行。进行放射性核素肺灌注研究，以检测肺血管的变化。免疫组织化学方法检测巨噬细胞、组织缺氧(碳酸氢酶-9标志物)、氧化应激(8-羟基-2‘-脱氧鸟苷)、促纤维化因子(转化生长因子-β)和促血管生成因子(血管内皮生长因子[VEGF])的表达。结果：照射后3d，肺血流灌注随组织缺氧而发生明显变化。照射后1周检测到明显的氧化应激，而巨噬细胞在4周开始聚集。TGF-β在照射后第1天表达显著增加，在照射后2周表达显著增加。低氧、氧化应激和这两种细胞因子的水平在照射后随着时间的推移继续上升。结论：肺血流灌注的早期改变是辐射后低氧和慢性氧化应激的始动因素。组织缺氧与巨噬细胞的激活和活性氧的持续产生有关，刺激纤维化和血管生成细胞因子的产生，维持慢性放射性肺损伤的发展。(C)2007年爱思唯尔公司。
Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury.Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2 '-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-beta [TGF-beta]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines.Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected I week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-beta expression was seen within I day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation.Conclusions: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury. (c) 2007 Elsevier Inc.